Researchers have developed and validated a model that predicts relapse in women with stage 2 or 3 breast cancer who have been treated with endocrine therapy prior to surgical removal of the tumor, according to a study published online September 23 in the Journal of the National Cancer Institute. The preoperative endocrine prognostic index (PEPI) may help identify women who can safely avoid chemotherapy and those women at high risk of relapse who should be considered for aggressive therapy.

Oncologists increasingly treat women with stage 2 and 3 estrogen receptor (ER)-positive breast cancer with endocrine therapy, such as tamoxifen or letrozole, prior to surgery to shrink the tumor. Researchers have not known whether a woman’s response to such therapy correlated with her risk of relapse in the future.

In the current analysis, Matthew Ellis, Ph.D., of the Washington University School of Medicine in St. Louis and colleagues examined surgical tumor samples from two previous studies in which women received endocrine treatment for several months prior to surgery. The team analyzed tumor samples from posttreatment surgery for ER status, histological grade, pathological grade, tumor size, nodal stage, treatment response, and Ki67 expression level, which is an indicator of cell proliferation. They tested these characteristics for an association with relapse-free survival and overall survival in 158 women treated in the P024 neoadjuvant trial and used the data to develop PEPI. They validated the model in 203 women previously treated in another clinical trial known as IMPACT.

Pathological tumor stage, nodal status, Ki67 expression level, and ER status in posttreatment specimens were independently associated with relapse-free survival; the PEPI model incorporates these characteristics. PEPI was a statistically significant predictor of relapse-free survival in the women in the IMPACT study. None of the women with the lowest PEPI score in the IMPACT trial had relapsed during the follow-up period, which was a median of 60.3 months. The researchers need longer follow-up data to validate PEPI’s ability to predict overall survival.

“Of particular note, patients with low pathological stage (stage 1 or 0) and a favorable biomarker profile (PEPI score 0) at surgery had such a low rate of relapse that further adjuvant systemic therapy beyond continuation of an endocrine agent appears unnecessary,” the authors write. “In striking contrast, patients with high pathological stage disease at surgery and a poor biomarker profile (PEPI group 3) had a statisti¬cally significant higher risk of early relapse, more typical of ER [negative] disease, and therefore should be offered all appropriate adjuvant treatments available.”

Given the robust associations, the researchers suggest that prospective validation of the model is warranted. If validated in a prospective manner, PEPI could help guide individual treatment and assess novel endocrine therapies in future clinical trials.

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Contact: Joni Westerhouse, .(JavaScript must be enabled to view this email address), (314) 286-0120

Citation: Ellis MJ, Tao Y, Luo J, et al. Outcome Prediction for Estrogen Receptor–Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics. J Natl Cancer Inst 2008; 100:1380?

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